A comparison of neonatal outcomes after taking progesterone pills and progesterone intramuscular injections in preterm labor: An RCT


Background: Approximately two-thirds of infant mortality within the first year of life are caused by preterm labor (PL).

Objective: This study aimed to investigate the effects of progesterone-based compounds to prevent PL.

Materials and Methods: This randomized clinical trial study was conducted on 146 pregnant women admitted to Department of Obstetrics and Gynecology, Afzalipour hospital in Kerman University of Medical Sciences, Iran in June 2019. The participants with PL received Tocolytic and 12 mg Betamethasone in 2 doses over 2 days to mature the fetus’s lungs. Stopping PL was considered a 12-hr period without any contractions after finishing the Tocolytic. Following the successful cessation of PL, the participants were monitored for 48 hr. Subsequently, the participants were divided into 2 groups. Participants received 200 mg Lutogel capsules orally per day in group A while group B received a weekly dose of 250 mg Proluton in the form of intramuscular injection, respectively. Treatment in groups continued until the 36th wk of delivery. The participants were followed-up weekly, and if any signs of PL were detected, an obstetrician carried out a vaginal examination.

Results: The incidence of PL was the same in both groups. There was no significant difference in the latent phase, average birth weight, and the neonatal intensive care unit admission frequency (p = 0.07, 0.17, 0.58, respectively) between groups.

Conclusion: No difference in the results obtained from the neonatal outcomes evaluated in groups. Both medications similarly led to recovering pregnancy and neonatal outcomes caused by PL. Applying the oral form with similar beneficial effects were pointed out in this study, which can be a solution to the issues caused by numerous injections that are inevitable in the injected administration of this medicine.

Key words: Obstetric labor, Premature, Progesterone, Oral, Injections.


[1] Mastantuoni E, Saccone G, Gragnano E, Spiezio Sardo AD, Zullo F, Locci M, et al. Cervical pessary in singleton gestations with arrested preterm labor: A randomized clinical trial. Am J Obstet Gynecol MFM 2021; 3: 100307.

[2] Mol BW, Wood S, Rode L, Tabor A, Aboulghar MM, Porcher R, et al. Evaluating progestogens for preventing preterm birth international collaborative (EPPPIC): Meta-analysis of individual participant data from randomised controlled trials. Obstet Gynecol Survey 2021; 76: 464–466.

[3] Mathew S, Kumar A. A prospective analysis of the risk factors and the perinatal outcome of preterm labour. Int J Reprod Contracept Obstet Gynecol 2018; 7: 4833–4839.

[4] Jarde A, Lutsiv O, Beyene J, McDonald SD. Vaginal progesterone, oral progesterone, 17-OHPC, cerclage, and pessary for preventing preterm birth in at-risk singleton pregnancies: An updated systematic review and network meta-analysis. BJOG 2019; 126: 556–567.

[5] Stewart LA, Simmonds M, Duley L, Llewellyn A, Sharif S, Walker RA, et al. Evaluating progestogens for preventing preterm birth international collaborative (EPPPIC): Meta-analysis of individual participant data from randomised controlled trials. Lancet 2021; 397: 1183–1194.

[6] Zierden HC, Ortiz JI, DeLong K, Yu J, Li G, Dimitrion P, et al. Enhanced drug delivery to the reproductive tract using nanomedicine reveals therapeutic options for prevention of preterm birth. Sci Transl Med 2021; 13: eabc6245.

[7] Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, et al. A randomized trial of progesterone in women with bleeding in early pregnancy. N Engl J Med 2019; 380: 1815–1824.

[8] Devine K, Richter KS, Widra EA, McKeeby JL. Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with endometrin have inferior ongoing pregnancy rates: Results from the planned interim analysis of a three-arm randomized controlled noninferiority trial. Fertil Steril 2018; 109: 266–275.

[9] Jarde A, Lutsiv O, Park CK, Beyene J, Dodd JM, Barrett J, et al. Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: A systematic review and network meta-analysis. BJOG 2017; 124: 1176–1189.

[10] Wood SL, Williams BN, Szychowski JM, Owen J. The effect of intramuscular 17α-hydroxyprogesterone in women screened for shortened cervical length. Am J Perinatol 2020; 37: 659–665.

[11] Abdelaziz MH. Oral versus vaginal progesterone in preterm labor. Evid Based Women’s Health J 2017; 7: 141–149.

[12] Ashoush S, El-Kady O, Al-Hawwary G, Othman A. The value of oral micronized progesterone in the prevention of recurrent spontaneous preterm birth: A randomized controlled trial. Acta Obstet Gynecol Scand 2017; 96: 1460–1466.

[13] Choudhary M, Suneja A, Vaid NB, Guleria K, Faridi MMA. Maintenance tocolysis with oral micronized progesterone for prevention of preterm birth after arrested preterm labor. Int J Gynecol Obstet 2014; 126: 60–63.

[14] Rai P, Rajaram S, Goel N, Gopalakrishnan RA, Agarwal R, Mehta S. Oral micronized progesterone for prevention of preterm birth. Int J Gynecol Obstet 2009; 104: 40–43.

[15] Gonzalez-Quintero VH, Istwan NB, Rhea DJ, Smarkusky L, Hoffman MC, Stanziano GJ. Gestational age at initiation of 17- hydroxyprogesterone caproate (17P) and recurrent preterm delivery. J Matern Fetal Neonatal Med 2007; 20: 249–252.

[16] Borna S, Sahabi N. Progesterone for maintenance tocolytic therapy after threatened preterm labour: A randomised controlled trial. Aust N Z J Obstet Gynaecol 2008; 48: 58–63.

[17] O’Brien JM. 17-hydroxyprogesterone caproate, progesterone, preterm birth prevention, and safety: Who decides? Someone should. Am J Obstet Gynecol 2011; 204: e16–e17.